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Biomedical subjects

N Rushton

Publications and source records attributed to N Rushton.

At least 73 records · Page 4Linked to original sources

Accuracy of DEXA measurement of bone mineral density after total hip arthroplasty.

Dual-energy X-ray absorptiometry (DEXA) is increasingly used to measure changes in bone mineral density (BMD) around femoral prostheses after total hip arthroplasty. We have studied the factors which affect the accuracy of these measurements. The coefficient of variation was < 2% using a hydroxyapatite phantom, 2.7% in an anthropomorphic phantom specimen, and < 1% in repeated measurements on implanted cadaver femora. The precision did not vary with different implant materials or designs. In patients we found a mean precision error of 2.7% to 3.4%. The most significant factor affecting reproducibility was rotation of the femur. We conclude that DEXA is a precise method of measurement for small changes in BMD around femoral implants, but that correct and careful positioning of patients is essential to obtain reliable results.

Absorptiometry, Photon↗

Toxicity of particulate silicon carbide for macrophages, fibroblasts and osteoblast-like cells in vitro.

There is widespread interest in the use of interfacial layers in the preparation of diamond and diamond-like carbon (DLC) coatings. These DLC coatings deposited onto metal substrates with a silicon carbide (SiC) interfacial layer exhibit improved adhesion and show promise as wear-retardant coatings for biomedical implants. Although the DLC coatings show excellent biocompatibility in vitro, they may be susceptible to damage within the biological environment, leading to exposure of the interfacial silicon carbide. We have investigated the effects of two forms of silicon carbide (alpha-SiC and beta-SiC) on macrophages, fibroblasts and bone cells in vitro. Both alpha- and beta-SiC are well-tolerated by cells at concentrations of up to 0.1 mg/ml but cause severe cytotoxicity at a concentration of 1 mg/ml. If SiC is to be used as an interfacial layer on biomedical implants, the quality of the DLC coating must be optimised to minimise the risk of film breakdown.

Adhesiveness↗

The effects of lactic acid on PGE2 production by macrophages and human synovial fibroblasts: a possible explanation for problems associated with the degradation of poly(lactide) implants?

The aim of this study was to investigate the effects of lactic acid on cells found at the bone-implant interface in order to try to discover more about the effects of degradation of implants manufactured from poly(lactide). This study shows that human synovial fibroblasts and murine macrophages release prostaglandin E2 (PGE2) a bone resorbing and inflammatory mediator, into the surrounding medium when exposed to lactic acid. The production of PGE2 in response to lactate may help to explain isolated cases of inflammation and discomfort seen some time after fracture fixation with poly(lactide) implants.

Animals↗

The effects of diamond-like carbon coatings on macrophages, fibroblasts and osteoblast-like cells in vitro.

The elaboration of metallic and polymeric particles from the wear of joint replacement components is widely implicated in the pathogensis of aseptic loosening of these implants. Diamond-like carbon (DLC) coatings show great potential as wear-retardant coatings and may offer a possible solution to this problem. We have studied the effects of DLC coatings on cells derived from the tissues that surround a total joint replacement (macrophages, fibroblasts and osteoblast-like cells). There was no evidence that DLC coatings, deposited on a variety of different substrates, caused cytotoxicity in vitro. Cells grown on the coated substrates exhibited normal cellular growth and morphology. DLC coatings are biocompatible in vitro and should now be tested in animal models to determine their behaviour in vivo.

Animals↗

Lactate dehydrogenase activity as a rapid and sensitive test for the quantification of cell numbers in vitro.

Lactate dehydrogenase (LDH) has been used extensively as a marker for cell death both in vitro and in vivo. The release of LDH into tissue culture medium accurately reflects cell viability in vitro. We have investigated the relationship between cell concentration and total LDH activity in samples of cell lysate. Although there are differences in the amount of LDH present in different cell types, the total enzyme activity in a sample of cell lysate is directly proportional to the concentration of cells in the sample. The measurement of LDH activity in vitro provides a sensitive, accurate and cost-effective alternative to the use of either radioisotopic or dye-based assays for the determination of cell numbers.

Animals↗

A rapid, quantitative assay for measuring alkaline phosphatase activity in osteoblastic cells in vitro.

Alkaline phosphatase (ALP) is the most widely recognized biochemical marker for osteoblast activity. Although its precise function is poorly understood, it is believed to play a role in skeletal mineralization. The aim of this study was to develop an assay suitable for measuring the activity of this enzyme in microtiter plate format. Using the well-characterized osteoblast-like cell line Saos-2, this paper describes an optimized biochemical assay suitable for measuring ALP activity in tissue culture samples. We have determined that a p-nitrophenyl phosphate substrate concentration of 9 mM provides highest enzyme activities. We have found that cell concentration, and hence enzyme concentration, affects both the kinetics and precision of the assay. We also tested several methods of enzyme solubilization and found that freeze-thawing the membrane fractions twice at -70 degrees C/37 degrees C or freeze-thawing once with sonication yielded highest enzyme activities. The activity of the enzyme decreased by 10% after 7 days storage. This assay provides a sensitive and reproducible method that is ideally suited for measuring ALP activity in isolated osteoblastic cells, although sample preparation and storage can influence results.

Alkaline Phosphatase↗

A comparative study of peri-prosthetic bone mineral density measurement using two different dual-energy X-ray absorptiometry systems.

24 patients aged 38-72 years with an uncemented total hip arthroplasty had dual-energy X-ray absorptiometry of the upper femur performed at a mean of 27 months after surgery. Each patient was scanned on both Lunar DPX and Hologic QDR-1000 densitometers. Peri-prosthetic bone mineral density (BMD) around the femoral component was measured in seven Gruen zones using software analysis techniques to allow quantification of bone mineral adjacent to a metal implant. There was a high correlation between the results obtained with the two systems (r = 0.94). BMD measurements using the Lunar DPX were 11% higher than with the Hologic QDR; however, there was a lack of agreement between the two instruments indicating that the two methods may not be used interchangeably.

Absorptiometry, Photon↗

Biocompatibility of particulate polymethylmethacrylate bone cements: a comparative study in vitro and in vivo.

The biocompatibility of particles of four different commercial polymethylmethacrylate (PMMA) bone cements was evaluated by exposing human synovial fibroblasts and mouse peritoneal macrophages to particles of cement. Cell integrity and inflammatory potential were assessed using enzyme release and microscopical examination. Results suggested the occurrence of cell damage in both cell types and macrophage studies indicated inflammatory potential. The response in vivo was investigated by intra-articular injection of the particles into mouse knee joints. Clinical and histological evaluation was performed over 2-52 wk. Particles of all four cements were well tolerated in the joints.

Acetylglucosaminidase↗

Mediators of bone resorption around implants.

An important cause of prosthetic loosening is bone resorption that results from the interaction of macrophages with implant surfaces and particulate debris. The mediators involved in this bone resorption were investigated in vitro. Medium conditioned by macrophages interacting with foreign materials was assayed for bone resorption stimulation and inhibition, and for prostaglandin E2 (PGE2). In some experiments, the medium was dialyzed, and in others indomethacin was added. Macrophages were found to release stimulators and inhibitors of bone resorption. The relative amount of these was variable. When macrophages interacted with foreign surfaces, their stimulatory effect was ten times their inhibitory effect. Further activation by phagocytosis caused a further 15-fold increase in stimulation, with no change in inhibition. It is probable that before macrophages encounter foreign materials their stimulatory and inhibitory effects are the same so that they do not cause net bone resorption. Important stimulatory and inhibitory mediators were not dialyzable and so were probably cytokines or possibly collagenase. Prostaglandins were neither important stimulators nor inhibitors. There was only enough PGE2 released to account for 2% of the bone resorption that was stimulated.

Animals↗

Biocompatibility of particles of GORE-TEX cruciate ligament prosthesis: an investigation both in vitro and in vivo.

This research was to determine the biocompatibility of simulated wear particles from a GORE-TEX cruciate ligament prosthesis using in vitro and in vivo techniques. Exposure of normal human synovial fibroblasts and primary mouse peritoneal macrophages to the particles revealed no cytotoxicity, as determined by lactate dehydrogenase release, but beta-N-acetyl-D-glucosaminidase was released from macrophages at high concentrations, showing inflammatory potential. This was not seen when the particles were injected into mouse knees, where no adverse reactions were observed. These simulated wear particles were shown to be biocompatible using these in vitro and in vivo systems.

Acetylglucosaminidase↗

Biocompatibility of diamond-like carbon coating.

Diamond-like carbon coating is an inert, impervious hydrocarbon coating with properties suitable for use in the biomedical field, particularly in orthopaedic implants. Mouse peritoneal macrophages and mouse fibroblasts were grown on tissue culture plates treated with diamond-like carbon and the biocompatibility assessed both biochemically and morphologically. This investigation showed that diamond-like carbon coating caused no adverse effects on cells in culture and therefore merits further investigation as a coating for biomedical use.

Animals↗

Bone density distribution within the femoral head and neck. An examination by high-resolution computed tomography.

The upper portions of three cadaveric femora were examined by high-resolution computed tomography. Analysis of the resulting images provided both quantitative and spatial distributions of bone density within the femoral head and neck. The information obtained provides new insights into aspects of proximal femoral architecture for both normal and osteoporotic bone. The study also points the way towards a clinical technique for measuring the material properties of proximal femoral bone.

Absorptiometry, Photon↗

The effect of strain on bone cell prostaglandin E2 release: a new experimental method.

A new method of investigating the mechanisms of strain-induced bone remodeling has been developed. Bone cells were subjected to cyclical strains in vitro by computer-controlled stretching of the plastic substrate on which they were cultured, enabling both physiological and pathological strains to be investigated. Physiological strains have not previously been investigated in vitro. The prostaglandin E2 (PGE2) released by the cells was found to depend on the strain magnitude. It was independent of cycle time, and 5 hours after straining had ceased, it had returned to control levels. These results are similar to the in vivo findings that bone remodeling is dependent on strain magnitude and not strain frequency, indicating that PGE2 may play an important role in strain-induced bone remodeling. The relationship between PGE2 release and strain magnitude was biphasic, with particularly high levels being released at strains that would be associated with either abnormally strenuous activity or microstructural bone damage. It is therefore possible that PGE2 stimulates the osteogenesis caused by increased functional demands, and initiates the remodeling caused by bone damage. This new method of investigating strain-induced remodeling is useful, as any cell type, any mediator, and any strain pattern or parameter can be individually studied.

Alkaline Phosphatase↗

Carbon fibre composite bone plates. Development, evaluation and early clinical experience.

We compared the mechanical properties of carbon fibre composite bone plates with those of stainless steel and titanium. The composite plates have less stiffness with good fatigue properties. Tissue culture and small animal implantation confirmed the biocompatibility of the material. We also present a preliminary report on the use of the carbon fibre composite plates in 40 forearm fractures. All fractures united, 67% of them showing radiological remodelling within six months. There were no refractures or mechanical failures, but five fractures showed an unexpected reaction; this is discussed.

Adult↗

Macrophages stimulate bone resorption when they phagocytose particles.

We investigated in vitro a mechanism by which particulate debris may induce bone resorption and cause implant loosening. We first studied two standard particles: latex, which is considered to be inert, and zymosan, which is inflammatory. Macrophages that phagocytosed either particle became activated, and stimulated 15 times as much bone resorption as did control macrophages. For activation to occur, 100 times more latex than zymosan had to be phagocytosed. We also found that bone cement and polyethylene particles activated macrophages in a similar manner, and that the necessary amounts of these were intermediate between those of latex and zymosan. None of the particles were toxic. It was concluded that implant loosening may result from bone resorption stimulated by mediators released by macrophages that have phagocytosed particles of bone cement or polyethylene.

Animals↗

Tennis elbow. A clinicopathologic study of 22 cases followed for 2 years.

Twenty-two elbows in 20 patients with persistent lateral pain due to epicondylitis had release of the common extensor origin and decortication of the lateral epicondyle. Specimens taken from the lateral epicondyle were examined histologically and compared with controls, and patients were reviewed clinically 2 (1/2-4) years after operation. Following surgery, symptoms were improved in 17 patients. Histologic examination of the bone-tendon junction revealed evidence of a repair response of variable degree, the most frequent features being mucopolysaccharide infiltration and bone formation. Fibrofatty degenerative changes were also present in some cases. There was no correlation between the intensity of the histologic reaction and the clinical outcome.

Adult↗

Hook-pin fixation of subcapital fractures of the femur: an atraumatic procedure?

Eighty-seven patients with subcapital fractures of the femur treated by hook-pin fixation were reviewed clinically and radiologically with an average follow-up time of 29 months. There were 58 undisplaced and 29 displaced fractures. Seven per cent of the undisplaced and 31 per cent of the displaced fractures developed avascular necrosis (AVN) and failure of fixation was seen in 3.5 per cent and 10 per cent respectively. Overall, 23 per cent of patients developed healing complications of which just over one-half had revision arthroplasty. The AVN rate in the undisplaced group was relatively low, though there was no clear advantage over simple screw fixation. In contrast, the incidence of AVN in displaced fractures was higher than with other methods. Fixation failure was related to surgical error in most instances.

Adult↗

Proximal femoral surface strain gauge analysis of a new epiphyseal prosthesis.

This paper describes a new type of proximal femoral, replacement arthroplasty and its preliminary, pre-clinical, evaluation. The prosthesis was designed as a replacement for the femoral capital epiphysis. It comprises a thin, metal, articular shell and an underlying 'epiphyseal' replacement which is modulus-matched to adjacent proximal femoral bone. Surface strain gauge analysis of the proximal femur under conditions simulating static single leg stance demonstrated that the new prosthesis maintains an essentially normal femoral strain distribution. It is hoped that selective load transmissions across the prosthesis-bone interface should result in less post-implantation proximal bone resorption.

Hip Prosthesis↗